The general objective of the proposed studies is to identify and characterize the molecular mechanisms underlying proximal tubular transport of bicarbonate at the basolateral side of the cell. This would include investigating adaptive alterations in the properties of the identified basolateral membrane bicarbonate transport pathways associated with chronic metabolic and respiratory acidosis. A glucocorticoid hormone requirement for the adaptive expression of altered basolateral bicarbonate transport in response to chronic acidosis will be examined. Preparations of plasma membrane vesicles isolated from the basolateral surface of rat proximal tubular cells will be used to study mechanisms of bicarbonate transport. The mechanism by which bicarbonate exists the cell across the proximal tubule basolateral membrane may be by passive conductance driven by the more than adequate electrical potential difference spanning this membrane. Alternatively, the translocation of bicarbonate may occur as an electrogenic or electroneutral carrier mediated mechanism coupled to the flow of other ions. It is the specific aim of the proposed studies to identify and characterize ion-coupled transport pathways for bicarbonate and how the properties of these transport mechanisms are altered as an expression of the renal acidosis induced adaptive response. The problem of defining membrane mechanisms regulating intracellular pH is of fundamental significance in understanding the etiology of many disease processes. In this regard the results of the proposed studies will be relevant to a variety of cell types in addition to kidney.